Tumour necrosis factor (TNF) is involved in the pathophysiology of sepsis and TNF is thus a promising therapeutic target in human sepsis trials. Research into the molecular mechanisms underlying sepsis has unexpectedly suggested that an existing class of drugs used to treat erectile dysfunction (ED) may be beneficial
By studying a mouse model of sepsis, researchers at the University of Pittsburgh, Pennsylvania, discovered that administering sildenafil, a phosphodiesterase-5 inhibitor, caused the liver to produce more cyclic GMP, which in turn reduced TNF signalling in hepatocytes and prevented liver damage.
“Sildenafil and other ED drugs might be a good approach to try early in the course of the illness to forestall organ damage,” says Timothy Billiar, the study’s senior author.
 Deng M, Loughran PA, Zhang L et al. Shedding of the tumor necrosis factor (TNF) receptor from the surface of hepatocytes during sepsis limits inflammation through cGMP signaling. Science Signaling 2015; 8(361):ra11.